Department of Membrane Transport, Division BIOCEV, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Department of Membrane Biochemistry, Institute of Animal Biochemistry and Genetics, Centre of Biosciences of the Slovak Academy of Sciences, Bratislava, Slovakia.
Cell Microbiol. 2019 Dec;21(12):e13093. doi: 10.1111/cmi.13093. Epub 2019 Aug 14.
Naturally occurring antimicrobial peptides and their synthetic analogues are promising candidates for new antifungal drugs. We focused on three groups of peptides isolated from the venom of bees and their synthetic analogues (lasioglossins, halictines and hylanines), which all rapidly permeabilised the plasma membrane. We compared peptides' potency against six pathogenic Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei and C. dubliniensis) and the non-pathogenic model yeast Saccharomyces cerevisiae. Their activity was independent of the presence of the multidrug-resistant pumps of C. glabrata but was influenced by the lipid composition of cell plasma membranes. Although the direct interaction of the peptides with ergosterol was negligible in comparison with amphotericin B, the diminished ergosterol content after terbinafine pretreatment resulted in an increased resistance of C. glabrata to the peptides. The tested peptides strongly interacted with phosphatidylglycerol, phosphatidic acid and cardiolipin and partly with phosphatidylinositol and phosphatidylethanolamine. The interactions between predominantly anionic phospholipids and cationic peptides indicated a mainly electrostatic binding of peptides to the membranes. The results obtained also pointed to a considerable role of the components of lipid rafts (composed from sphingolipids and ergosterol) in the interaction of yeast cells with the peptides.
天然存在的抗菌肽及其合成类似物是新型抗真菌药物的有前途的候选物。我们专注于从蜜蜂毒液中分离出的三组肽及其合成类似物（lasio 肽、halictines 和 hylanines），它们都能迅速使质膜穿孔。我们比较了这些肽对六种致病性念珠菌（白色念珠菌、光滑念珠菌、近平滑念珠菌、热带念珠菌、克柔念珠菌和都柏林念珠菌）和非致病性模式酵母酿酒酵母的效力。它们的活性不依赖于光滑念珠菌的多药耐药泵的存在，但受细胞质膜脂质组成的影响。尽管与两性霉素 B 相比，肽与麦角固醇的直接相互作用可以忽略不计，但特比萘芬预处理后麦角固醇含量降低导致光滑念珠菌对肽的耐药性增加。测试的肽与磷脂酰甘油、磷脂酸和心磷脂强烈相互作用，并与磷脂酰肌醇和磷脂酰乙醇胺部分相互作用。主要带负电荷的磷脂与阳离子肽之间的相互作用表明肽与膜之间主要通过静电结合。所得结果还表明，脂筏的成分（由鞘脂和麦角固醇组成）在酵母细胞与肽相互作用中起着相当大的作用。
